Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice

• Published in: Cardiovascular research 2006-06, Vol.70 (3), p.457-465
• Main Authors: Matsusaka, Hidenori, Ide, Tomomi, Matsushima, Shouji, Ikeuchi, Masaki, Kubota, Toru, Sunagawa, Kenji, Kinugawa, Shintaro, Tsutsui, Hiroyuki
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Echocardiography; Female; Gene Deletion; Heart Rupture, Post-Infarction - metabolism; Heart Rupture, Post-Infarction - physiopathology; Heart Rupture, Post-Infarction - prevention & control; Heterozygote; Male; Matrix Metalloproteinases - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Animal; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Oncogene Protein v-akt - metabolism; Time Factors; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - physiopathology; Ventricular Remodeling
• ISSN: 0008-6363
• DOI: 10.1016/j.cardiores.2006.02.001

Apoptosis may play an important role in cardiac remodeling after myocardial infarction (MI). p53 is a well-known proapoptotic factor. However, its pathophysiological significance in these conditions remains unclear. We thus examined the effects of target deletion of the p53 gene on post-MI hearts. Anterior MI was created in male heterozygous p53-deficient (p53(+/-); n = 28) mice and sibling wild-type (p53(+/+); n = 29) mice by ligating the left coronary artery. By day 7, p53(+/-) mice had significantly better survival rate than p53(+/+) mice (89% vs. 69%, P < 0.05). Notably, p53(+/-) mice had a significantly lower incidence of left ventricular (LV) rupture (7% vs. 28%, P < 0.05) despite comparable infarct size (60 +/- 2% vs. 59 +/- 2%, P = NS), heart rate (488 +/- 15 vs. 489 +/- 17 bpm, P = NS), or mean arterial blood pressure (80 +/- 2 vs. 78 +/- 3 mm Hg, P = NS). The extent of infiltrating interstitial cells including macrophages into the post-MI hearts was not altered by the deletion of p53. Further, collagen deposition as well as the zymographic MMP-2 and -9 activities were comparable between p53(+/-) and p53(+/+) mice with MI. However, the p53(+/-) mice had a significantly thicker infarct wall. The number of TUNEL-positive cells in the infarct area was significantly lower in p53(+/-) mice than in p53(+/+) mice (423+/-86 vs. 1330 +/- 275/10(5) cells, P < 0.01). p53 is involved in cardiac rupture after MI, probably via the induction of a proapoptotic pathway. The inhibition of p53 may be a potentially useful therapeutic strategy to manage post-MI patients.